Voltage-gated ion channels are a diverse family of integral membrane proteins that provide a pathway for physiologically relevant ions to cross the cell membrane. Thus, they are fundamental for many cellular processes including electrical excitability in nerve and muscle cells. In this project we are concerned with determining a molecular picture of channel structure and function. We will isolate a large collection of new ion channel cDNAs by the methods of DNA cross-hybridization and polymerase chain reaction amplification. Primary amino acid sequences of channels will be deduced;. and functional features will be determined by the Xenopus oocyte expression system. From structure-function comparisons we hope to define better the extent of channel subfamilies in terms of the structures encoded and the functions represented. We anticipate that these comparisons will allow us to correlate functional differences with particular portions of channel primary amino acid sequence. We propose to test these correlations by constructing hybrid channels and using the Xenopus oocyst system as assay.